The Research Of Combined Drug Delivery System Of Lipid-coated Hollow Mesoporous Silica Nanopheres For Doxorubicin And Paclitaxel On A549 Lung Cancer Cells

ObjectiveThe study was to prepare the carrier of lipid-coated hollow mesoporous silica nanopheres(L-HMSN)for doxorubicin and paclitaxel and study the mechanism of the drug-loaded system on A549 cells.MethodsThe hollow mesoporous silica nanospheres were prepared by template method,and the phospholipids were coated on the surface of the sphere by the lipid film hydration method in order to obtain the carrier L-HMSN.Doxorubicin and paclitaxel were used as model drugs.Doxorubicin by adsorption method was adsorbed into the hollow structure of L-HMSN,and paclitaxel with phospholipids by the lipid film hydration method was wrapped on the surface of hollow mesoporous silica nanoparticles.The drug delivery system(DOX/PTX@L-HMSN)was finally prepared.The methods of transmission electron microscopy(TEM),differential scanning calorimetry(DSC),X-ray diffraction(XRPD)and fourier transform infrared spectroscopy(FTIR)were used to characterize the drug loading system.The cell experiment was used to evaluate the biological safety of L-HMSN,and the effect of drug loading system on lung cancer A549 cells was investigated.The effect of carrier on the release rate of two drugs was investigated by release test in vitro,and the pharmacokinetics of rabbit in vivo was studied.ResultsThe characterization results showed that doxorubicin and paclitaxel in the nanopheres were present in an amorphous state.The results of a vitro release test showed that the two drugs in the delivery system achieved slow release.The cell uptake experiments demonstrated that L-HMSN was successfully internalized into A549 cells.In addition,the combination of doxorubicin and paclitaxel in the drug delivery system showed a significant synergistic effect on the inhibition of A549 cell growth.The pharmacokinetic in vivo studies showed that L-HMSN achieved the drug combination of doxorubicin and paclitaxel,and improved the drug efficacy.ConclusionThe results showed that L-HMSN can not only avoid the interaction of two drugs,but also realize the drug combination,regulate the drug release and improve the drug efficacy.In addition,L-HMSN was a good drug carrier because of its high specific surface area,large pore volume,adjustable pore structure,surface modification and so on.Therefore,L-HMSN,as a carrier of two drugs,had a great prospect for the combined delivery system.